Research at the WCGRC has the objectives (a) to collect, store, retrieve, and analyze phenotypic, genealogic and epidemiological data on congenital anomalies and genetic diseases and to speed the identification of previously undescribed genetic disorders of man and to establish their phenotypic spectrum and natural history; (b) to perform collaborative research on accumulated epidemiological, genealogical, twin, linkage and other data, and on the phenotypic cytogenetic, anatomical, pathological and biochemical aspects of congenital and chronic disease in order to define the genetic cause and pathogenesis underlying human genetic disorder, and to improve means of pre and postnatal detection, treatment and prevention of such conditions; and (c) to teach in this clinical research setting basic and medical genetics to medical and graduate students, house-officers, postdoctoral fellows and practicing physicians. Specifically this includes clinical, anatomical, pathological, biochemical, cytogenetic studies of infants and children with single major malformations, malformation syndromes, newly recognized hereditary conditions, mental retardation, certain cancers and intersexuality. Many previously and recently identified chromosome abnormalities are being studied with banding techniques to determine breakage sites and to assist in chromosome mapping; the biochemical basis of hematopoiesis is being studied in Tfm mice. A census and health survey of Iowa, Wisconsin, Illinois, Missouri and Minnesota Old Order Amish populations is being updated and newly recognized genetic disorders in that population are being studied and reported. Studies on a sample of some 1500 severely retarded individuals are being continued and a complte population survey for MR in Burnett Co., WI has been initiated. Cancer studies involve cytological marker and transformation investigations, and studies of the importance of unstable premutation as a cause of human syndromes and cancers. Studies of X-chromosome abnormalities, prenatal diagnosis and amniotic cells are continuing.